The majority of proteins are made of 20 different α-amino acids: Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Glutamine, Glutamate, Phenylalanine, Glycine Histidine, Isoleucine, Lysine, Leucine, Methionine, Proline, Serine, Threonine, Tryptophan, Tyrosine and Valine.
However, there are many biologically active peptides comprising other amino acids such as: Homocysteine, Ornithine, 4-Hydroxyproline, 5-Hydroxylysine, Selenocysteine, Formylmethionin, Phosphoserine, Acetylserine, Methylarginine etc.
Amino acids in D-configuration are common in non-ribosomally synthesized bacterial peptides and less common in ribosomally synthesized proteins. For example in the non-ribosomally synthesized Bacitracins, the amino acid residues in positions 4, 7, 9 and 11 are usually in D-configuration (Glu, Orn, Phe and Asp).
Bacitracins are peptide antibiotics naturally produced by Bacillus subtilis and Bacillus licheniformis. Several Bacitracins have been identified of which Bacitracin A is of primary importance and is highly active (Biochemistry, vol. 39 no 14, 2000, page 4037-45 by Epperson and Ming). The primary structure of Bacitracin A is NH2-L-Ile1-L-Thiazoline2-L-Leu3-D-Glu4-L-Ile5-L-Lys6-D-Orn7-L-Ile8-D-Phe9-L-His10-D-Asp11-L-Asn12-COOH which is cyclized between the ε-amino group of L-Lys6 and the R-carboxyl group of L-Asn12.
Several non-ribosomally synthesized peptides comprise unusual amino acids. For example cyclosporin A comprises 2(S)-amino-3(R)-hydroxy-4(R)-methyl-6(E)-octenoic acid which is crucial for binding to the intracellular receptor for cyclophilin, and thus for its immunosuppressive activity (Journal of Biological Chemistry, vol. 268 no 35, 1993 by Offenzeller et al).
Several uncommon amino acids resemble the structure of Isoleucine:                2-Amino-5-methyl-5-hexenoic acid, a new methionine analog, was isolated from a fermentation broth of Streptomyces (Journal of Antibiotics vol. 32 no. 11, page 1118-1124, 1979 by Takeuchi et al).        4 methylene-norleucine and 2-aminohept-6-enoic acid are compounds with the formula: C7H13NO2.        4 methyl-norleucine is an isoleucine derivative which can be incorporated into a recombinant protein. (J Pharm Biomed Anal, vol 31. no. 5, 2003, page 979-987 by Muramatsu et al).        2-amino-3-methyl-4-pentenoic acid is an unsaturated isoleucine analogue which can be incorporated into proteins (Chembiochem vol. 7 no. 1, 2006, page 83-87 by Mock et al).        The unsaturated norleucines of Amanita solitaria. Chemical and pharmacological studies (Lloydia vol. 36 no. 2, 1973, page 69-73 by Chilton et al).        Beta-methylnorleucine, an antimetabolite produced by Serratia marcescens (J Antibiot, vol. 34 no. 10, 1981 page 1278-82 by Sugiura et al)        U.S. Pat. No. 6,168,912 describes various allyl derivatives of amino acids for use in a multidimensional combinatorial chemical library.        Allylglycine and crotylglycine are described in Journal of Bacteriology, vol. 148 no. 1, 1981 by Kunz et al.        